I. Field of the Invention
This invention concerns a process for the preparation of streptovaricin having a high production efficiency.
II. Description of the Prior Art
Five types of streptovaricins are known, designated as A, B, C, D, and E, (U.S. Pat. No. 3,116,202). Initially, they drew attention because of their usefulness as an antituberculosis antibiotic. Recently, it has been found that derivatives obtained by chemically modifying streptovaricins, and particularly, Streptovaricin C, are useful as anti-retroviral agents, anti-cancer agents or the like. See Japanese published pre-examination patent application No. 110,000/1979.
A known process for the preparation of streptovaricins comprises fermenting a submerged culture of Streptomyces spectabilis, U.S. Pat. No. 3,116,202. However, this preparation process has a low productive efficiency and only a very small amount of streptovaricin was obtained. The apparent reason is that the produced streptovaricin is rapidly decomposed in the medium. Moreover, because the streptovaricin produced has a high lipid solubility, it accumulates on the surface of the hyphae which suppresses production. Therefore, this process is difficult to use industrially. A method has been disclosed wherein a nonionic resin has been added to the fermentation both for clycloheimide fermentation. However, this resulted in only a two to three fold improvement in production efficiency. See H. Wang, Annuals New York Academy of Sciences, 431, 1483, pp. 313-321.